Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, 700107, Kolkata, West Bengal, India.
Out Patient Department, Manovikas Kendra Rehabilitation and Research Institute for the Handicapped, 700107, Kolkata, West Bengal, India.
J Mol Neurosci. 2023 May;73(4-5):237-249. doi: 10.1007/s12031-023-02113-2. Epub 2023 Mar 21.
Despite several efforts to identify the causes of autism spectrum disorders (ASD), its etiology remains still unclear. Among other aspects, genes that encode neurotransmitter receptors are strong candidates for autism. Here, we wanted to study some genetic variants of gamma-aminobutyric acid (GABA) receptor subunit genes GABRB3, GABRG3, and GABRA5, located on chromosome 15q11-q13 that might contribute to the etiology of ASD in the affected children of West Bengal. rs7180158, rs2081648 (GABRB3); rs12910555 (GABRG3); rs35399885, rs35832850 (GABRA5) were analyzed in 316 children with ASD and 227 healthy controls. Phenotypic associations were evaluated by Childhood Autism Rating Scale (CARS). Gene expression levels were measured by quantitative real-time PCR. ASD probands showed a higher frequency of "A" allele for rs7180158, "G" allele for rs12901555, and "T" allele for rs35399885. The GA + AA genotypes (rs7180158) and CT + TT genotypes (rs35399885) were found to confer significant risk towards ASD. rs2081648 was found to have transmission bias in the family. Additionally, these variants were found to be associated with one or more of ASD-associated phenotypic traits. Multifactor dimensionality reduction (MDR) analyses showed mostly independent contributory effects of some of the variants. Again, the gene expression levels of GABRB3, GABRG3, and GABRA5 were downregulated in the cases than the controls. ForGABRA5 rs35399885, the CC genotypes corresponded to higher expression levels compared to the other groups. This study reveals that genetic variants of GABA receptor subunit genes are significantly associated with ASD. No data for the mentioned variants are found in the population of West Bengal, India.
尽管已经做出了很多努力来寻找自闭症谱系障碍（ASD）的病因，但它的发病机制仍然不清楚。在其他方面，编码神经递质受体的基因是自闭症的重要候选基因。在这里，我们想研究一下位于 15q11-q13 染色体上的γ-氨基丁酸（GABA）受体亚基基因 GABRB3、GABRG3 和 GABRA5 的一些遗传变异，这些变异可能与西孟加拉邦自闭症儿童的病因有关。rs7180158、rs2081648（GABRB3）；rs12910555（GABRG3）；rs35399885、rs35832850（GABRA5）在 316 名自闭症儿童和 227 名健康对照中进行了分析。采用儿童自闭症评定量表（CARS）评估表型相关性。采用实时定量 PCR 测量基因表达水平。自闭症患者 rs7180158 的“A”等位基因、rs12901555 的“G”等位基因和 rs35399885 的“T”等位基因频率较高。GA+AA 基因型（rs7180158）和 CT+TT 基因型（rs35399885）被发现与 ASD 显著相关。rs2081648 在家族中存在传递偏倚。此外，这些变异与一个或多个自闭症相关表型特征有关。多因子降维分析（MDR）显示，一些变异的独立贡献作用较大。同样，GABRB3、GABRG3 和 GABRA5 的基因表达水平在病例中低于对照。对于 GABRA5 rs35399885，CC 基因型与其他组相比，表达水平更高。这项研究表明，GABA 受体亚基基因的遗传变异与自闭症显著相关。在印度西孟加拉邦的人群中没有发现这些变异的相关数据。
